Monday, 10 March 2014

Long-acting HIV drug shows promise

Two
new sets of research show that regular injections of an antiretroviral drug
protects macaques monkeys from simian-human immunodeficiency virus infection. The
research has raised hopes that preventing HIV infection in humans will soon be
as easy as a shot in the arm four times a year. Researchers are optimistic that
the findings could one day lead to a new generation of HIV drugs for infected people.

The
medication has been developed by researchers from Rockefeller University,
GlaxoSmithKline, and the Tulane National Primate Research Center. The new drug
is termed a "integrase strand-transfer inhibitor GSK744", and it has
been developed as a long-acting injectable, designed to be administered every
three months.

GSK744
(also known as S/GSK1265744) is an investigational new drug under development
for the treatment of HIV infection. Integrase inhibitors are a class of
antiretroviral drug designed to block the action of integrase, a viral enzyme
that inserts the viral genome into the DNA of the host cell. Integrase
inhibitors were initially developed for the treatment of HIV infection, but
they could also be applied to other retroviruses. GSK744 works by interfering
with the enzyme that HIV uses to insert its DNA into the human genome. This
blocks the key step needed for the AIDS virus to replicate itself, and the
viral DNA simply degrades inside the cell.

In
investigational studies, the GSK744 agent has been packaged into nanoparticles
(GSK744LAP) conferring an exceptionally long half-life of 21–50 days following
a single dose. In theory, this would make possible suppression of HIV with
dosing as infrequently as once every three months. Animal studies indicate that
this theory is getting closer to reality.

Based
on a report in the journal Science, the drug has
led to monkeys, infected with a virus very similar to HIV called simian-human
immunodeficiency virus (SHIV), becoming protected. The study, by Chasity
Andrews and colleagues is titled "Long-Acting Integrase Inhibitor Protects
Macaques from Intrarectal Simian/Human Immunodeficiency Virus".

For
the study, Andrews and her colleagues studied sixteen rhesus macaques. The
monkeys were challenged with SHIV. After this, eight monkeys received placebo and eight were
administered with GSK744 (where the drug was injected intramuscularly). All eight
macaques who received GSK744 remained averimic (that means without SHIV),
during both the rectal challenge phase and during the subsequent follow-up ten-week
examination phase. In contrast, all eight macques who received placebo were
infected with SHIV during the challenge phase.

For
the next phase of the study, the researchers aim to carry out similar tests
where they will determine the minimum protective dose of GSK744 that is
required in order to stop SHIV from replicating and multiplying.

Remarkably,
a second research team from the U.S. Centers for Disease Control and Prevention
(CDC) have found a similar effect when studying GSK744 in female monkeys.

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With
the new HIV research findings, both research groups have presented their
results to the U.S. Centers for Disease Control and Prevention (CDC) annual
Conference on Retroviruses and Opportunistic Infections, which held in Boston
this week.

Commenting
on the research findings, The New York
Times
explains: “If the findings can be replicated in humans, they have the potential
to overcome a major problem in AIDS prevention: that many people fail to take
their antiretroviral pills regularly."

In
short, this could be the first step towards an HIV vaccine. In the meantime, ‘pre-exposure
prophylaxis’ with drugs used to treat the infection has become one of the most
promising strategies to cut down HIV infection rates among high-risk
populations. On this basis the newly developed drug for monkeys could, within a
short space of time, be turned into a long-acting injectable drug for people
and one that could improve upon current treatments. Furthermore, since
integrase inhibitors target a distinct step in the retroviral life cycle, they
may be taken in combination with other types of HIV drugs to minimize
adaptation by the virus. They are also useful in salvage therapy for patients
whose virus has mutated and acquired resistance to other drugs.

The
main obstacle for realizing a version effective against HIV is likely to be
keeping up the treatment regime. Philip
Johnson of the Children’s Hospital of Philadelphia in Pennsylvania told the
science site Science Now. “This is going
to require multiple injections over the lifetime of an individual,” he said,
asking: “How feasible is it truly in the long term?”

Much
more likely it seems that having to make multiple pills each day for HIV. GSK744
injections have the potential to overcome a major problem in AIDS prevention:
that many people fail to take their antiretroviral pills regularly.